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Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein

Contributors

Boergeling, Yvonne; Rozhdestvensky, Timofey S; Schmolke, Mirco; Resa-Infante, Patricia; Robeck, Thomas; Randau, Gerrit; Wolff, Thorsten; Gabriel, Gülsah; Brosius, Jürgen; Ludwig, Stephan

Published in

PLOS pathogens, vol. 11, no. 5, e1004924

Publication date

2015

Abstract

Influenza A virus (IAV) defective RNAs are generated as byproducts of error-prone viral RNA replication. They are commonly derived from the larger segments of the viral genome and harbor deletions of various sizes resulting in the generation of replication incompatible viral particles. Furthermore, small subgenomic RNAs are known to be strong inducers of pattern recognition receptor RIG-I-dependent type I interferon (IFN) responses. The present study identifies a novel IAV-induced defective RNA derived from the PB2 segment of A/Thailand/1(KAN-1)/2004 (H5N1). It encodes a 10 kDa protein (PB2∆) sharing the N-terminal amino acid sequence of the parental PB2 protein followed by frame shift after internal deletion. PB2∆ induces the expression of IFNβ and IFN-stimulated genes by direct interaction with the cellular adapter protein MAVS, thereby reducing viral replication of IFN-sensitive viruses such as IAV or vesicular stomatitis virus. This induction of IFN is completely independent of the defective RNA itself that usually serves as pathogen-associated pattern and thus does not require the cytoplasmic sensor RIG-I. These data suggest that not only defective RNAs, but also some defective RNA-encoded proteins can act immunostimulatory. In this particular case, the KAN-1-induced defective RNA-encoded protein PB2∆ enhances the overwhelming immune response characteristic for highly pathogenic H5N1 viruses, leading to a more severe phenotype in vivo.

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UNIGE research groups

Citation (ISO format)

BOERGELING, Yvonne et al. Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein. In: PLOS pathogens, 2015, vol. 11, n° 5, p. e1004924. doi: 10.1371/journal.ppat.1004924

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

1553-7366
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301downloads

Technical informations

Creation

17/09/2015 14:57:00

First validation

17/09/2015 14:57:00

Update

14/03/2023 23:42:54

Status update

14/03/2023 23:42:53

Last indexation

31/10/2024 01:34:45
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